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Abstract Film capacitors are playing an increasingly important role in power‐related fields, driven by the continuous development of dielectric materials and practical needs. Long‐term accumulation has also led to an increasing wealth of data related to film capacitors. Sonification opens up a new way for people to make good use of data from film capacitors. A framework for sonifying film capacitors data based on TwoTone is presented. Based on the analysis and discussion, it is clear that the sonification results can easily represent the monotonic variation pattern of film capacitors data. What's more, the sonification results increase the possibility that people pay attention to the changing trend of film capacitors data when there is no significant difference in the visual perception of the data. In addition to providing a new way of music generation of electrical equipment, the method proposed is expected to contribute to theory reference in typical scenarios, such as factory calibration of film capacitors, monitoring of film capacitor operation status, and presentation of statistical data of film capacitors' dielectric materials, which will help us to better understand the distribution characteristics of polymer films.

Background Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin‐based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high‐dose and moderate‐dose statins for patients who had experienced mild ischemic stroke during the acute period. Methods and Results This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high‐intensity and moderate‐intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow‐up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high‐intensity statin and moderate‐intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85–1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86–1.34]; P=0.519). High‐intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00–3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10–3.16]; P=0.021). The results from the propensity score‐matched analyses were consistent with those from the Cox proportional hazards analysis. Conclusions Compared with moderate‐intensity statin therapy, high‐dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. Registration URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Abstract Background The biomarkers of immune checkpoint inhibitors in the treatment of non‐small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. Methods From February 2017 to November 2020, pretreatment and on‐treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. Results We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). Conclusion ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Abstract Background The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations. Methods We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen‐induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed. Results The result indicated that there are striking OVA dose‐related differences in antigen‐induced AHR to MCh. The most intense antigen‐induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium. Conclusion Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols.

Abstract Roegneria yenchiana sp. nov. (Triticeae) is a new species collected from Shangri‐la of Yunnan Province in China based on morphological, cytological, and molecular data. It is morphologically characterized by one spikelet per node, rectangular glums, awns flanked by two short mucros in lemmas, distinguished from other species of Roegneria. The genomic in situ hybridization results indicate that R. yenchiana is an allotetraploid, and its genomic constitution is StY. Phylogenetic analyses based on multiple loci suggested that R. yenchiana is closely related to Pseudoroegneria and Roegneria, and the Pseudoroegneria served as the maternal donors during its polyploid speciation.

Objective. To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods. We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results. In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07–1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08–1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04–1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02–1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07–1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61–0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions. Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Abstract The human microbiome plays a crucial role in maintaining health, with advances in high‐throughput sequencing technology and reduced sequencing costs triggering a surge in microbiome research. Microbiome studies generally incorporate five key phases: design, sampling, sequencing, analysis, and reporting, with sequencing strategy being a crucial step offering numerous options. Present mainstream sequencing strategies include Amplicon sequencing, Metagenomic Next‐Generation Sequencing (mNGS), and Targeted Next‐Generation Sequencing (tNGS). Two innovative technologies recently emerged, namely MobiMicrobe high‐throughput microbial single‐cell genome sequencing technology and 2bRAD‐M simplified metagenomic sequencing technology, compensate for the limitations of mainstream technologies, each boasting unique core strengths. This paper reviews the basic principles and processes of these three mainstream and two novel microbiological technologies, aiding readers in understanding the benefits and drawbacks of different technologies, thereby guiding the selection of the most suitable method for their research endeavours.

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole‐exome sequencing (WES) and T‐cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non‐silent mutations from multi‐samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi‐cancers. IHC using antibodies against CD4, CD8, and PD‐L1 demonstrated scant T‐cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T‐cell clones shared across tumor regions in any of the patients, while over 94% of T‐cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi‐regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T‐cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.

The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC‐a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm‐level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large‐scale SCNAs as rich sources of bladder cancer clonal diversities. The prevalence of TP53 and ATM clonal mutations as well as the associated burden of SCNAs is significantly higher in Whites/Blacks than in Asians. We identify a trans‐ancestry prognostic subtype of bladder cancer characterized by enrichment of non‐muscle‐invasive patients and muscle‐invasive patients with good prognosis, increased CREBBP/FGFR3/HRAS/NFE2L2 mutations, decreased intra‐tumor heterogeneity and genome instability, and an activated tumor microenvironment.

Abstract As the current multi‐segment signal fusion algorithms cannot meet the requirement of high‐precision frequency estimation at different signal‐to‐noise ratios (SNRs), an adaptive fusion algorithm is proposed in this paper. At high SNR, an autocorrelation weighted fusion algorithm is utilised, which adopts the real‐time weighted fusion of multi‐segment autocorrelation signals, resulting in denoised sinusoidal signals. Then the frequency is obtained by minimising the error function based on coarse estimation. At low SNR, an improved spectrum fusion algorithm is adopted, which uses the three‐parameter sine‐fitting method to determine the phase difference compensation factor, and the multi‐segment signal spectrum is weighted to obtain a long signal spectrum with continuous phase. As a result, the frequency can be estimated by spectral peak search. Simulation results show that the proposed algorithm, compared with existing algorithms, not only improves the estimation accuracy by about 20%–50% but also can perform high‐precision frequency estimation for multi‐segment signals of different lengths, frequencies, and abnormal situations.

Abstract Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation of phospholipids. Interactions of iron and lipid metabolism factors jointly promote ferroptosis. Ferroptosis has been demonstrated to be involved in the development of various diseases, such as tumors and degenerative diseases (e.g., aortic dissection), and targeting ferroptosis is expected to be an effective strategy for the treatment of these diseases. Recent studies have shown that the regulation of ferroptosis is affected by multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, and protein posttranslational modifications. Epigenetic changes have garnered considerable attention due to their importance in regulating biological processes and potential druggability. There have been many studies on the epigenetic regulation of ferroptosis, including histone modifications (e.g., histone acetylation and methylation), DNA methylation, and noncoding RNAs (e.g., miRNAs, circRNAs, and lncRNAs). In this review, we summarize recent advances in research on the epigenetic mechanisms involved in ferroptosis, with a description of RNA N6‐methyladenosine (m6A) methylation included, and the importance of epigenetic regulation in biological processes and ferroptosis‐related diseases, which provides reference for the clinical application of epigenetic regulators in the treatment of related diseases by targeting ferroptosis.

Nociceptors are kinds of sensory neurons that send warning information to the central nervous system in response to noxious stimuli. Thermal nociception happens as the thermal stimulus exceeds 45 °C as this temperature is perceived to be potentially harmful. Simulating this function is of great significance to developing bioinspired electronic skins and humanoid robots, which thus creates more demands for electronic devices that can simulate thermal nociception. Herein, an artificial thermal nociceptor (ATN) is fabricated by integrating a temperature sensor and a synaptic transistor, which can simulate the thermal pain threshold of the human body and operates in a very similar way as the transient receptor potential vanilloid 1 (TRPV1). For this ATN, the function of temperature sensing is realized by a graphite–polydimethylsiloxane (Gr–PDMS) composite temperature sensor, and the synaptic functions, as well as nociceptor features, are emulated through a synaptic transistor using xanthan gum polysaccharide electrolyte as gate dielectric, providing energy‐efficient building blocks for brain‐inspired computation systems. In a word, the ATN proposed can help to open a new avenue and provides more possibilities in the design of artificial sensory systems with the functions of temperature perception and thermal feedback.

Abstract Background Starting with low metastatic capability, T4N0M0 (diameter ≥ 7 cm) non‐small cell lung cancers (NSCLCs) constitute a unique tumor subset, as with a large tumor size but no regional or distant metastases. We systematically investigated intratumoral heterogeneity, clonal structure, chromosomal instability (CIN), and immune microenvironment in T4N0M0 (≥7 cm) NSCLCs. Methods Whole‐exome sequencing, RNA sequencing, and multiplex immunohistochemistry (mIHC) staining were conducted to analyze 24 spatially segregated tumor samples from eight patients who were pathologically diagnosed with T4N0M0 (diameter ≥ 7 cm) NSCLCs. The adjacent normal tissues and peripheral blood served as controls. Results In total, 35.2% of mutations and 91.1% of somatic copy number alterations were classified as subclonal events, which exhibited widespread genetic intratumoral heterogeneity. In contrast, a low degree of CIN was observed. None of the patients had genome doubling. The burden of loss of heterozygosity, aneuploidy, and the genome instability index of these tumors were significantly lower than those in the TRACERx cohort. Expression profiles revealed significantly upregulated expression of cell division‐related signals and the G2/M checkpoint pathway. In addition, a similar expression pattern of the immune microenvironment was observed in different regions of the tumor, which was confirmed by mIHC profiles. Conclusions Our study indicates the presence of intratumoral genetic heterogeneity and immune microenvironmental heterogeneity features in T4N0M0 NSCLCs, and the low degree of CIN may be related to the low metastatic capability.

Homozygous deletion (HD) of CDKN2A and CDKN2B (CDKN2A/BHD) is the most frequent copy‐number variation (CNV) in lung adenocarcinoma (LUAD). CDKN2A/BHD has been associated with poor outcomes in LUAD; however, the mechanisms of its prognostic effect remain unknown. We analyzed genome, transcriptome, and clinical data from 517 patients with LUAD from the Cancer Genome Atlas (TCGA) and from 788 primary LUAD tumor and matched control samples from the MSK‐IMPACT clinical cohort. CDKN2A/BHD was present in 19.1% of the TCGA‐LUAD cohort and in 5.7% of the MSK‐IMPACT cohort. CDKN2A/BHD patients had shorter disease‐free survival and overall survival compared with CDKN2A/BWT individuals in both cohorts. Differences in clinical features did not influence the outcomes in the CDKN2A/BHD population. Mutation analyses showed that overall tumor mutational burden and mutations in classical drivers such as EGFR and RB1 were not associated with CDKN2A/BHD. In contrast, homozygous deletion of type I interferons (IFN‐IHD) frequently co‐occurred with CDKN2A/BHD. CDKN2A/B and IFN‐I are co‐located in the same p21.3 region of chromosome 9. The co‐occurrence of CDKN2A/BHD and IFN‐IHD was not related to whole‐genome doubling, chromosome instability, or aneuploidy. Patients with co‐occurring CDKN2A/BHD and IFN‐IHD had shorter disease‐free survival and overall survival compared with CDKN2A/BWT patients. CDKN2A/BHDIFN‐IHD had downregulated several key immune response pathways, suggesting that poor prognosis in CDKN2A/BHD LUAD could potentially be attributed to an immunosuppressive tumor microenvironment as a result of IFN‐I depletion.

This paper presents a methodology for actively discovering knowledge in transport hotline databases by analyzing complaints reported by citizens, aiming to assist transportation management departments in planning actions to investigate and improve service quality. The proposed model uses text mining techniques and applies latent Dirichlet allocation (LDA) to identify topics that are related to transportation services. Consequently, we actively analyzed over 230,000 phone calls occurring in a certain province between 1st January and 31st December 2021. Specifically, we actively analyzed nearly 22,000 phone calls about the taxi industry within a selected city, and identified six topics, including lost and found (27.1%), car blocking (20.6%), attitude and behavior (17.1%), online car-hailing (12.8%), illegal operations (11.2%), and fare issues (11.2%). By actively referring to past and ongoing best practices, we actively recommend several policy implications. The proposed method thus actively transforms the service center record into a customer feedback-based assessment system to intently monitor drivers’ professionalism while efficiently addressing customers’ complaints and concerns.

Growth hormone (GH), which is commonly considered to be a promoter of growth and development, has direct and indirect effects on adult gonads that influence reproduction and sexual function of humans and nonhumans. GH receptors are expressed in adult gonads in some species including humans. For males, GH can improve the sensitivity of gonadotropins, contribute to testicular steroidogenesis, influence spermatogenesis possibly, and regulate erectile function. For females, GH can modulate ovarian steroidogenesis and ovarian angiogenesis, promote the development of ovarian cells, enhance the metabolism and proliferation of endometrial cells, and ameliorate female sexual function. Insulin-like growth factor-1 (IGF-1) is the main mediator of GH. In vivo, a number of the physiological effects of GH are mediated by GH-induced hepatic IGF-1 and local IGF-1. In this review, we highlight the roles of GH and IGF-1 in adult human gonads, clarify potential mechanisms, and explore the efficacy and the risk of GH supplementation in associated deficiency and assisted reproductive technologies. Besides, the effects of excess GH on adult human gonads are discussed as well.

Objective. The effect of physiological dose growth hormone (GH) replacement therapy on bone mineral density (BMD) in adults with growth hormone deficiency (GHD) is not well defined. We aimed to investigate the effects of 18 months of treatment with recombinant human growth hormone (rhGH) at physiological doses on BMD, body composition (BC), and quality of life (QoL). Methods. Sixty-eight patients diagnosed with adult growth hormone deficiency (AGHD) in our hospital were included in this retrospective study. All patients received individualized rhGH replacement to maintain normal serum insulin-like growth factor-1 (IGF-1) levels. BMD and BC measurements were performed by dual energy X-ray absorptiometry (DXA). Excluding those with incomplete follow-up data, we analyzed BMD in 68 patients, as well as BC and QoL in 36 of them. Results. Compared with the baseline, lumbar spine BMD decreased by 0.008 g/cm2 (P=0.006) and increased by 0.011 g/cm2 (P=0.045) at month 18, and total hip BMD decreased by 0.005 g/cm2 (P=0.008) and did not change significantly from the baseline at month 18. The changes in BMD did not differ by sex, and the increase in BMD was more pronounced in patients with low Z-scores at the baseline (lumbar spine: P=0.005 and total hip: P=0.018). The percentage change from the baseline in BMD was greater for the lumbar spine than for the total hip (P=0.003). Lean body mass (LBM) increased significantly (P=0.012), total body fat ratio (TBF%) decreased significantly (P=0.011), visceral adipose tissue (VAT) decreased significantly (P=0.016), and QoL improved significantly (P

Abstract Ergothioneine (EGT) represents valuable protective functions for humans, but EGT from the diet cannot meet daily requirements. Although the heterologous synthesis of EGT had been achieved, it is still a challenge to obtain stable and high‐yield EGT‐producing cell factories. Here, after the co‐overexpression of the EGT synthetic gene cluster and hisG, hisC, and allB1 in Mycolicibacterium neoaurum, the natural EGT titer was increased by 7.2‐folds. However, the degradation problem of EGT in large‐scale fermentation needs to be urgently solved. A putative lyase gene Mn_3042 was inactivated, thus inhibiting the product degradation and increasing the EGT titer by 21%. Moreover, the enhancement of S‐adenosyl‐ l‐methionine regeneration further increased EGT titer by 28%. After optimization of fed‐batch fermentation, the yield of EGT was boosted to 1.56 g/L with a productivity of 7.2 mg/L/h. This study provides a systematic engineering strategy for developing EGT‐producing cell factories.

Objective To investigate the effect of platelet‐rich plasma on tendon‐bone healing after anterior cruciate ligament reconstruction. Methods This retrospective study included 85 patients (range, 18–50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet‐rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively. Results The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet‐rich plasma group than in the normal saline group at all follow‐up time points (P

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P=0.007), especially in nonischemic HF. Log2‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r=−0.25, P

The primary objective of this study was to develop and validate an efficient and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach as a means to detect tropifexor plasma concentrations in beagle dogs and to study its pharmacokinetic profile in beagle dogs. The chromatographic separation of tropifexor and oprozomib (internal standard, ISTD) on the column, with the addition of acetonitrile for rapid precipitation and protein extraction, was achieved with 0.1% formic acid aqueous solution-acetonitrile for the mobile phase. A Xevo TQ-S triple quadrupole tandem mass spectrometer, under the selective reaction monitoring (SRM) mode, for the determination of the concentrations in the positive ion mode. The mass transfer pairs of tropifexor and oprozomib (ISTD) were m/z 604.08 ⟶ 228.03 and m/z 533.18 ⟶ 199.01, respectively. The profile displayed well linearity with calibration curves for tropifexor and oprozomib (ISTD) ranging from 1.0 to 200 ng/mL. In parallel, the lower limit of quantification (LLOQ) value for tropifexor could be measured with the aid of this novel technique at 1.0 ng/mL. In addition, the scope of intraday and interday for analyte accuracy was between −4.86% and 1.16%, with a precision of 88.13% and were free of significant matrix effects. The stability met the requirements for the quantification of plasma samples under various conditions. Finally, the pharmacokinetic profile of tropifexor in beagle dog plasma following oral administration of 0.33 mg/kg tropifexor was determined by using the method facilitated in this work.

The transition from surface mining to underground is a critical issue for metal mines. The commonly cited procedure cored by ultimate-pit-limit (UPL) methodology is restricted to maximize the profit from both surface and underground mining, due to the absence of the integration of the profit from either of them. Under the target for such maximization, this study proposes a new optimization approach, which directly relates the design of open-pit limit and underground stopes, by equalizing the marginal profit from either surface or underground mining. The variation of the crown pillar size is involved in this approach. The proposed approach is applied to the Dagushan iron mine, and results show the total profit increased from 3.79 billion CNYs (original design by conventional UPL methodology) to 4.17 billion CNYs (optimal design by the proposed approach), by 9.91%. Moreover, the marginal profit from surface and underground mining, as well as total profit, of all possible designs of surface-to-underground mining transition in Dagushan iron mine is calculated to validate the proposed approach. When the marginal profits satisfy the criterion of the proposed approach, the maximum value of the total profit appears, and this demonstrates the proposed approach is robust to maximize the total profit in surface-to-underground mining transition. This work contributes to existing literature studies primarily from practical aspect, by providing a unified approach to optimize the transition from surface to underground mining.

The traditional offline marketing mode of agricultural products was relatively single and difficult to adapt to the effective communication between agricultural and commercial enterprises and customers under the new situation, while the coordination between online agricultural products marketing management and customers’ consumption needs was not enough. Therefore, this paper puts forward the research on the construction of online agricultural product consumption demand analysis model based on data mining technology. Based on the supply-demand relationship between agricultural and commercial enterprises and consumers, this paper analyzed consumers and their demand behavior for agricultural products and gave an evaluation model of customers’ consumption demand for agricultural products. Using data mining technology, this paper made a cluster analysis on the characteristics of consumer demand behavior and established the mapping relationship between agricultural products and consumer demand. Then, the online consumption demand prediction and analysis model of agricultural products was put forward. Finally, the performance of demand forecasting model based on data classification was analyzed. The empirical results showed that the model proposed in this paper can better predict and analyze the consumption demand behavior of online agricultural products and had certain feasibility and effectiveness. The online consumption demand analysis model proposed in this paper played a positive role in improving the marketing management level of agricultural products.